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Biomedical subjects

M Handa

Publications and source records attributed to M Handa.

At least 163 records · Page 9Linked to original sources

Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation.

BACKGROUND: Shear-induced platelet aggregation (SIPA) is an important mechanism in thrombogenesis. von Willebrand factor (vWF) binding to platelet glycoprotein Ib (GP Ib) has been found to be crucial for platelet aggregation under the high shear force probably generated in stenosed coronary artery. The physiological significance of vWF-dependent SIPA has not been clarified. METHODS AND RESULTS: Blood samples were collected from 23 normal volunteers. SIPA was continuously monitored using a modified cone-plate viscometer adapted for measuring the transmitted light intensity of the material. The effects of low concentrations of epinephrine, ADP, and collagen on SIPA under both low shear (12 dyne/cm2) and high shear (108 dyne/cm2) force were investigated. All agonists tested enhanced SIPA under low shear force, whereas only epinephrine augmented SIPA under high shear force. The maximum extents of SIPA under high shear force in the absence and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/- 13.9%, respectively. The antagonist of the alpha 2-adrenergic receptor yohimbine (1 microgram/ml) antagonized the effects of epinephrine. The monoclonal antibody NMC-4 against vWF, which was shown to inhibit its binding to GP Ib, completely abolished SIPA under high shear force, even in the presence of epinephrine. However, this antibody only partially inhibited SIPA under low shear force. CONCLUSIONS: Our findings suggest that epinephrine is the agonist that enhances SIPA mediated by vWF through its specific receptor. This may be clinically important because occlusion of the coronary artery often occurs in stenosed atherosclerotic vessels under sympathetic stimulation.

Adrenergic alpha-Antagonists↗

[Platelet adhesion and adhesive proteins--how to measure the platelet adhesiveness].

We examined, platelet adhesive function in vivo by comparing the platelet retention rate (PRR) with other laboratory tests. In 71 patients, PRR did not correlate with bleeding time (BT), ristocetin-induced platelet agglutination (RIPA), vWF:AG, vWF:RCo, FVIII:C, fibrinogen, platelets counts or platelet aggregation tests. Among them, the coincidence rate of PRR with BT seems relatively better than that of other tests. In patients with Bernard-Soulier syndrome (BSS), PRR, RIPA and high shear-induced platelet aggregation (SIPA), measured using a cone-plate type instrument, were decreased, while platelet adhesion in a static system and SIPA at a low shear rate were normal. In patients with Glanzmann's thrombasthenia (TA), PRR and SIPA were decreased at both high and low shear rates, while RIPA and platelet adhesion were normal in a static system. In patients with deficient glycoprotein Ia/IIa complex which is one of the putative receptors for collagen, platelet adhesion in a static system is markedly decreased. In patients with von Willebrand disease, the pattern of platelet adhesion tests was similar to that of BSS patients, while in patients with afibrinogenemia, it was similar to that of TA patients except for SIPA at a high shear rate. The various experiments using monoclonal antibodies support these abnormalities. These findings, suggest that PRR is a suitable screening test, but further rapid and easy tests will be necessary to diagnose the defects of platelet adhesion at various shear rates.

Bleeding Time↗

[An experience of surgical treatment for catamenial pneumothorax with diaphragmatic and pulmonary endometriosis].

A case of catamenial pneumothorax with diaphragmatic and pulmonary endometriosis is presented. A 43-year-old, married woman had three times of recurrent right pneumothorax during the period from January to July on 1990. Each episode was apparently related to the onset of the menstruation suggesting catamenial pneumothorax. Right thoracotomy revealed a perforation of the diaphragm and five black spots on the visceral pleura. Involved portion both diaphragm and lung were excised. Microscopic examination of the excised specimens showed endometrial stroma in the diaphragm and subpleural layer of the lung. Although it has been postulated that intrathoracic endometriosis is a possible cause of the pneumothorax, very few cases have been reported in which pulmonary or pleural endometriosis was demonstrated histologically. Surgical and pathologic findings are documented discussing the relationship of both conditions in this report.

Diaphragm↗

[Primary effect of preoperative intra-arterial infusion chemotherapy in cervical cancer].

In order to obtain better prognoses for cervical cancer, we conducted preoperative intra-arterial (i.a.) infusion chemotherapy of CDDP in combination with AT-II pressor. Two courses of i.a. chemotherapy were performed for 67 patients with cervical cancer in stage IIb containing 54 squamous cell carcinomas and 13 adenocarcinomas before operation every 3 weeks. A histologically desirable effect in cervical lesion was obtained. A group given preoperative i.a. chemotherapy had a significantly lower rate of infiltration beyond uterus in comparison with 156 patients with 145 squamous cell carcinomas and 11 adenocarcinomas treated by surgery alone as the control group. Further, the rate of histological infiltration to parametrial edges after i.a. chemotherapy tended to be lower than the control group. From the above, it was considered that preoperative i.a. infusion chemotherapy of CDDP in combination with AT-II pressor for cervical cancer was effective as a neo-adjuvant chemotherapy.

Adenocarcinoma↗

[Efficacy of leukocyte-depleted platelet concentrates for prevention of HLA-alloimmunization in patients with frequent platelet transfusions: a prospective multi-institutional study using a polyester platelet filter].

A prospective multi-institutional study was conducted to assess the efficacy of leukocyte-depleted platelet concentrates, prepared by a method using a newly developed polyester filter, in the prevention of HLA-alloimmunization in patients with hematological disorders. Patients who were expected frequent platelet transfusions, were assigned into two groups, receiving either standard platelet concentrates (control group) or leukocyte-depleted platelet concentrates prepared through a polyester platelet filter, Sepacell-PL (filtered group). All patients received leukocyte-depleted red cell products. Of III patients enrolled, 72 were evaluable, 23 in the control and 49 in the filtered group. Both groups were comparable according to age, sex ratio, underlying disorders, previous exposure to alloantigens by transfusion and/or pregnancy. There was no statistically significant difference in the number and duration of transfusion in the two groups. There were significant differences in HLA-alloimmunization rate (9 cases out of 23, 39% in the control group versus 4 cases out of 49, 8% in the filtered group; p less than 0.01) and refractoriness to platelet transfusion from random donors (6 cases out of 23, 26% in the control group versus 2 cases out of 49, 4% in the filtered group; p less than 0.05). These results indicated that leukocyte-depleted platelet concentrates prepared through the polyester platelet filter are beneficial to reduce HLA-alloimmunization in patients with frequent platelet transfusions.

Adolescent↗

[Detection of soluble forms of platelet membrane glycoproteins and its clinical significance].

Soluble forms of surface membrane glycoproteins of various cell types have been identified as makers for in vivo or in vitro cellular events, in which the receptors are involved. Using mouse monoclonal antibodies, sandwich ELISA systems to quantitate plasma concentrations of two platelet glycoproteins in soluble form were set up: one is glycocalicin (GC), a proteolytic fragment of GP Ib alpha chain and the other is GMP-140 or CD62 (GMP) known as a target for leukocyte recruitment at vascular injury sites. As in vivo markers, GC is said to reflect platelet turnover. High levels of plasma GMP were detected in patients with thrombotic thrombocytopenic purpura, being presumably indicative of microcirculation disorder. During storage of platelet concentrates, plasma levels of both markers were increased in a time-dependent fashion over 10 days. This correlated with a decrease in the surface expression of the glycoproteins on platelets, suggesting that the soluble glycoproteins entering the supernatants by proteolysis would be an useful indicator for in vitro alteration of stored platelets surface.

Biomarkers↗

[Abdominal complications of the pedicled omental flap in chest surgery].

The incidence of abdominal complications and the gastrointestinal function after omental pedicle wrapping (Group I: n = 13) were compared with those after right pneumonectomy (Group II: n = 9) and cholecystectomy (Group III: n = 22). Indications of the omentopexy were as follows: 1) prophylaxis for the bronchial complication after chest surgery (4 cases), 2) treatment of thoracic empyema (2 cases) and 3) postoperative bronchopleural fistula (7 cases). Poor intestinal movement necessitating fast after surgery persisted significantly longer in Group I than in Group II (p less than 0.05), but no significant difference was observed between Group I and Group III. Abdominal complications were observed frequently in Group I when oral feeding was initiated; abdominal distension in 7 of 13 cases (54%), epigastric discomfort in 3 (23%) and dehiscence of the abdominal wound in 4 (31%). Abdominal wound dehiscences were most frequently encountered after surgical treatment with the omentopexy for empyema thoracic (2/2, 100%) and for bronchopleural fistula (2/7, 28%). Upper GI examination was performed in seven cases, four of which (57%) showed the deformity of antral region of the stomach. Since this finding was not always accompanied with the symptom of gastric retention, it was likely that gastric retention following the omentopexy was caused by dissection of right gastroepiploic nerves rather than the anatomical deformity of the stomach.

Aged↗

[Prophylactic effect of ulinastatin on cisplatin-induced renal disorders in lung cancer patients].

In order to determine whether ulinastatin (US) can prevent renal dysfunction due to cisplatin (CDDP) or not, we comparatively studied serum BUN, serum creatinine (Cr), creatinine clearance (Ccr), urine gamma-glutamyl transpeptidase (gamma-GTP) excretion, urine N-acetyl-beta-D-glucosaminidase (NAG) excretion, fractional excretion of Na (FENa) and urine beta 2-microglobulin excretion between one group of 10 patients receiving single treatment with CDDP and another group of 10 patients receiving combination treatment with CDDP+US, in 20 subjects with primary lung cancer. In the US combination treatment group, urine gamma-GTP excretion, urine NAG excretion, and FENa elevation were significantly inhibited. Urine beta 2-microglobulin excretion was inhibited. In summary, US was considered to have a preventive effect against renal toxicity due to CDDP.

Aged↗

[Multicenter clinical evaluation of red cell concentrates stored up to 6 weeks in MAP, a new additive solution].

The clinical safety and efficacy of transfusion of red cell concentrates stored in MAP solution (MAP-CRC) containing mannitol, adenine, glucose, phosphate and citrate, into 39 anemic patients were evaluated. In 23 patients, infusion of MAP-CRC was alternated with infusion of ordinary CRC as a control. The MAP-CRC and CRC used in this study were stored at 4 degrees C for an average of 38.2 +/- 2.6 days (n = 52) and 18.1 +/- 2.2 days (n = 26), respectively. Red cell recovery was 77.5% for MAP-CRC and 82.5% for CRC, based on calculation of the increase in hemoglobin level one day after transfusion. There were no differences between patients transfused with MAP-CRC and those transfused with CRC in clinical findings or biochemical data. No major side-effects other than pyrexia associated with the underlying infections were seen in patients transfused with MAP-CRC. MAP-CRC stored up to 42 days is apparently as safe and effective as stored CRC. This new additive solution may therefore be useful for the future expansion of the indications for autologous blood transfusion by facilitating the collection and storage of more blood in the liquid state for a longer period, and may also be useful in obtaining more plasma from whole blood as source plasma.

Adenine↗

Repeated intestinal ulcerations in a patient with systemic lupus erythematosus and high serum antiphospholipid antibody levels.

We report the case of a patient with SLE who had repeated ulceration of the small intestine requiring emergency surgery. Pathologic examination revealed microthrombosis and vasculitis at the site of the intestinal ulcers. High levels of antiphospholipid antibodies, thrombocytopenia, and prolonged prothrombin time coincided with the episodes of intestinal ulceration. Antiphospholipid antibodies may be involved in the development of thrombosis resulting in the repeated episodes of intestinal ulceration in this patient. This possibility should be considered in patients with SLE who have intestinal ulceration and appropriate antithrombotic medication should be administered.

Adult↗

The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.

Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]o), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]o is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Willebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis.

Afibrinogenemia↗

Vasopressin and atrial natriuretic peptide release in cardiopulmonary denervated dogs.

To assess the effect of cardiopulmonary denervation on the release of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP), either hemorrhage (1.0 ml.kg-1.min-1, for 40 min) or an infusion of 3% dextran in lactated Ringer solution (RL) (3% dextran in RL, 1.0 ml.kg-1.min-1, for 40 min) was carried out in chronic cardiopulmonary denervated (CPD, n = 7) and sham-operated (SO, n = 7) dogs under anesthesia. Plasma AVP increased significantly in both groups during hemorrhage, but its rise was significantly attenuated in CPD dogs. Plasma ANP decreased similarly during hemorrhage in both groups. An infusion of 3% dextran in RL decreased significantly plasma AVP during its whole period in SO dogs, but AVP release was only suppressed in the late period in SO dogs. Plasma ANP increased significantly during its infusion in both groups. These results indicate that cardiopulmonary denervation may attenuate the release of AVP in response to either hemorrhage or blood volume expansion but may not affect the release of ANP in response to the blood volume change. Moreover, a large increase in plasma ANP may attenuate the release of AVP.

Animals↗